In the present study, a high resolution structure for the extramembranous regions of rhodopsin will be determined. The extramembranous domains will then be docked with the transmembrane helices of rhodopsin. At the present time, no high resolution structure is available for any G-protein receptor. Therefore, this study may provide the first such high resolution structure. These studies exploit the independent structural domains of the protein and represent an alternative method of determining integral membrane structure which may be generally applicable to membrane protein. Extensive literature on the independent stability of protein domains and the agreement between the structure determined here and measurements on intact rhodopsin supports this approach. Differential scanning calorimetry (DSC), circular dichroism (CD) and two-dimensional NMR will be used to determine the structures and stability of the protein domains. As rhodopsin is an integral membrane protein whose structure and function are influenced by the lipid bilayer, the role of both irreversibly-bound and reversibly-bound lipid on rhodopsin structure and stability will also be investigated. It is anticipated that this structure of rhodopsin will allow visualization of the binding site of transducin as well as the sites of phosphorylation. Furthermore, having determined the structure of the native rhodopsin, the structural consequences of mutations which are linked to autosomal dominant retinitis pigmentosa will be determined. These include mutations which are on both the extradiskal and intradiskal surfaces. Thus, rhodopsin structural defects could be linked to the disease state.